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The structures of takanawaenes A, B and C, novel antifungal antibiotics produced by Streptomyces sp. K99-5278, were elucidated by various spectroscopic analyses including UV and NMR, and spectrometric analyses including MS. They have the common skeleton of a 28-membered pentaene macrolide.

Three new pentaene macrolides having a 28-membered ring, designated takanawaenes A, B and C, were isolated from the fermentation broth of Streptomyces sp. K99-5278 by solvent extraction, silica-gel column chromatography and HPLC. Takanawaenes showed antifungal activity against Aspergillus niger, Mucor racemosus, Candida albicans and Saccharomyces cerevisiae.

A new microwave continuous sterilizer (MWS) for applying microwave dielectric heating as an alternative to an autoclave was developed. The developmental objectives of the MWS were: 1. Achieving sufficient sterilization for the drugs containing heat-sensitive ingredients. 2. Measuring and recording sterilization temperature of each ampoule. 3. Ensuring automatic continuous operation and linkage with the preceding and following machines in an injection ampoule production process. The temperature of the drug solution in an ampoule was heated to 140 degrees C within about 30 seconds by the MWS. Target F0 value is achieved through the maintaining heater to maintain the target temperature for 12 seconds. Ampoules are cooled with air and water after completion of heating. The MWS is capable of processing 150 ampoules per minute. The newly developed techniques which minimized temperature distribution of heated ampoule solution were: 1. Microwave irradiation in a direction opposite to the direction of ampoules transportation. 2. Microwave irradiation in the lower part of ampoule solution (i.e., heating up the drug solution by thermal convection.) 3. Microwave power control by feedback of measured temperatures. 4. Heating rate control corresponding to the dielectric property of ampoule solution. The drug stability test was performed using 3% pyridoxamine phosphate solution, and the inactivation of spores in 3% pyridoxamine phosphate solution was examined using Bacillus stearothermophilus ATCC 7953 spores. The MWS was proved to have an adequate efficiency of sterilization with less chemical degradation of the contents than an autoclave.

The activities and kinetic properties of argininosuccinate synthetase in cultured skin fibroblasts of three citrullinemic patients with qualitative or quantitative abnormalities of hepatic argininosuccinate synthetase were examined. The cultured skin fibroblasts of a citrullinemic patient with a low hepatic argininosuccinate synthetase activity showed low activity and abnormal kinetics similar to those of the hepatic enzyme. This suggests a similar genetic origin of the fibroblast argininosuccinate synthetase as of the hepatic enzyme. However, we found normal argininosuccinate synthetase activity in cultured fibroblasts of two citrullinemic patients who had a low hepatic enzyme activity resulting from decrease in the amount of enzyme protein but with normal kinetic properties. This suggests that part of the quantitative abnormality of hepatic argininosuccinate synthetase of citrullinemic patients may be due to an abnormal organ-specific gene expression in the liver.

A case of a 54-years-old female with pheochromocytoma associated with chronic renal failure is described. The patient was having hemodialysis preoperatively. For preoperative preparation, prazosin 12 mg.day-1 was used to control arterial pressure, and we increased the patient's dry weight by 0.5 kg. Anesthesia was maintained with 67% nitrous oxide, 33% oxygen and 1.0-2.0% enflurane. For intraoperative fluid management, we administered crystalloid solution 1 ml.kg-1.hr-1 and fresh frozen plasma 1600 ml. We simultaneously used phentolamine. The anesthesia was uneventful and the patient did well postoperatively.